Heparin-Induced Thrombocytopenia: A Case Presentation

Darcie Gampetro

Pharm.D Candidate 2011

September 2010

Patient JB

Pt is a 45 y.o. female who presents with acute respiratory failure. Pt was recently hospitalized for possible BOOP and concomitant pseudomonas

infection (9/5-9/10)– Medications upon discharge:

TMP/SMX Ciprofloxacin Voriconazole *On 9/11 platelet count was 220,000

Social History:– Lives with husband and 15 year old son– Has 27 year old daughter– 30-pack-year smoking history– History of alcoholism-currently sober for 2 months

Allergies– Doxycycline– Fentanyl– Hydoxyzine– Ketorolac– Nalbuphine– NSAIDs

Patient JB

Chest x-ray showed worsening of bilateral diffuse interstitial infiltrates Significant lab values:

– BP=168/124– Pulse=127 – Respiratory rate=44– O2 saturation=49%– WBC=20.1– Hgb=9.6– Hct=28.2– plt:=138,000 platelets/μL – Scr=1.7– BUN=35– Glucose=256– BNP=361

Review of Systems:– Mostly unobtainable as pt was placed on Bipap

Height: 66 in Weight: 72.9 kg pH 7.23, pCO2 57, pO2 67, bicarb 24

JB Past Medical History

Type I Diabetes Mellitus Bronchiolitis Obliterans Organizing Pneumonia (BOOP) Cirrhosis with liver decompensation and renal insufficiency related to

alcoholism—complicated by steatohepatitis, fribrosis and coagulopathy Depression with anxiety-previous suicide attempt with drug overdose Anorexia Chronic abdominal pain Pancreatitis in 2007 Carpal tunnel surgery C-section two times Cholescystectomy in 2007 Tubal ligation Adenoidectomy in 2006 Colonoscopy in 2008

Home Medications

Guaifenesin 600mg po daily Trimethoprim sulfamethoxazole

1 DS tab daily Prednisone 30 mg po daily Mylanta 30 mL po prn Magic mouthwash 30 mL po prn Voriconazole 200 mg po q12h Nicoderm 7 mg patch daily Methadone 60 mg po tid with

meals Ciprofloxacin 500 mg po bid Ursodiol 300 mg po tid Oxycodone 5 mg 2-3 tablets po

tid prn Omeprazole 40 mg po daily Vitamin E 1000 units po daily

Glucagon 1 mg subcutaneously one time as needed

Vitamin D 50,000 unitis po q 7 days

Lantus 32 units subcutaneously daily qam

Promethazine 25 mg tid prn Lorazepam 0.5 mg po bid prn Polyethylene glycol one 17 gm

packet po daily prn Metoclopramide 10 mg po qid

prn Multivitamin one tablet po daily Novolog correction scale

Inpatient Medications Day 1

Furosemide Methadone Lansoprazole Phyontadione Albuterol

Guaifenesin Propofol Hydromorphone Methylprednisolone Insulin Enoxaparin

Day 2 Medication Changes

Enoxaparin changed to heparin due to hepatic decompensation and renal insufficiency

Pipercillin/Tazobactam added Esomeprazole added Metoclopramide added

Day 4

4 doses of heparin given from 9/14-9/15 Platelets:

– 9/14: 104,000 platelets/μL– 9/15: 94,000 platelets/μL– 9/16:78,000 platelets/μL

Heparin-Induced Thrombocytopenia

Topic Discussion

Heparin-Induced Thrombocytopenia (HIT)

Decreased platelet count during or following heparin therapy

– <150,000 platelets/μL– 50% decrease from baseline

Onset may be rapid or delayed Mechanism of immune response

– Heparin binds to platelet factor 4 (PF4)

– IgG, IgM, and IgA antibodies generated

– Complexes aggregate and are prematurely removed from circulationthrombocytopenia

– Platelet activation leads to prothrombotic platelet microparticlespromotes coagulation

Two types of HIT– Type 1

Benign form Small decrease in platelet

count occurring two days after initiation of heparin (platelet count usually >100,000 platelets/μL)

Platelet counts return to normal with continued heparin therapy

– Type 2 More serious form of HIT Immune-mediated disorder

with formation of antibodies against heparin-PF4 complex

Risk of thrombosis

Figure taken from Uptodate (see references

Type 2 HIT

Factors strongly associated with development of HIT– Long duration of therapy ( >4 days)– Use of UFH– Surgery patients – Female rather than male pts

Thrombotic risk from HIT is more than 30x that of control population

Risk of thrombus remains high for days to weeks

Diagnosis of HIT

Rule out other causes of thrombocytopenia– Bacterial infection– Medications– Bone marrow disease

Laboratory Diagnosis– What abnormal values would we expect?

Pretest Probability of HITThe 4 T’s

Thrombocytopenia Timing of platelet count fall Thrombosis Other causes for thrombocytopenia present?

The 4 T’sThrombocytopenia

Platelet count fall > 50% and nadir >20,000: 2 points

Platelet count fall 30-50% or nadir 10-19,000: 1 point

Platelet count fall <30% or nadir <10,000: 0 points

The 4 T’sTiming of platelet count fall

Clear onset on days 5-10 or platelet count fall ≤1 day if previous heparin exposure within last 30 days:2 points

Not clear fall on days 5-10 (missing platelet counts) or onset after day 10 or fall ≤1 day with previous heparin exposure within last 30-100 days:1 point

Platelet count fall at <4 days without recent exposure:0 points

The 4 T’s Thrombosis or other sequelae

Confirmed new thrombosis, skin necrosis, or acute systemic reaction after IV UFH bolus: 2 points

Progressive or recurrent thrombosis, non-necrotizing skin lesions, or suspected thrombosis which has not been proven:1 point

None:0 points

The 4 T’sOther causes for thrombocytopenia present

None apparent: 2 points Possible: 1 point Definite: 0 points

The 4 T’s Score

Zero to 3: Low probability 4 to 5: Intermediate probability 6 to 8: High probability

Clinical Presentation

What are the clinical manifestations of HIT? Implications

– Mortality in 20-30% of patients with thrombosis – 20-30% of patients will become permanently

disabled

Treatment

Cessation of all formulations of heparin Alternative anticoagulation

– Lepirudin (Refludan®)– Bivalirudin (Angiomax ®)– Argatroban– Fondiparinux– Warfarin-once anticoagulated with other agent and platelets

>150,000/μL Duration of anticoagulation

– Two to three months if no thrombotic event occurred– Six months if thrombotic event occurred

Lepirudin (Refludan®)

Recombinant Hirudin Direct thrombin inhibitor FDA labeled indication: anticoagulation in patients with HIT and

associated thromboembolic disease in order to prevent further thromboembolic complications

Dosing: – Bolus: 0.4 mg/kg IVP over 15-20 seconds (max=44 mg)– Maintenance: 0.15 mg/kg/hr (16.5 mg/hr)– Reduce dose in renal impairment– Goal aPTT= 1.5-2.5 above baseline

For conversion to oral anticoagulant, must be above 1.5x aPTT and overlap therapies 4 to 5 days

Bivalirudin (Angiomax®)

Thrombin inhibitor FDA labeled indications: anticoagulant used in conjunction with

aspirin for patients with unstable angina undergoing percutaneous transluminal coronary angioplasty with provisional glycoprotein IIb/IIIa inhibitor; anticoagulant used in PCI or in patients at risk for HIT

Dosing:– Bolus: 0.75 mg/kg – Maintenance: 1.75 mg/kg/hr continuous infusion for up to 4 hours– If need further therapy, give 0.2 mg/kg/hr for up to 20 hours– Reduce dose in renal impairment

Argatroban

Direct thrombin inhibitor FDA labeled indications: prophylaxis or treatment of thrombosis

in patients with HIT; adjunct to percutaneous coronary intervention in patients who have or are at risk of thrombosis associated with HIT

Dosing:– 2mcg/kg/min IV– Goal aPTT at steady state is 1.5-3 times the initial baseline

value Can be used in patients with ESRD

Fondaparinux (Arixtra®)

Factor Xa inhibitor Not approved for use in HIT Dosing:

– 2.5 mg once daily

Long half life Renaly eliminated

Back to the case…

What tests should be done in this patient? What is our patients 4 T’s Score? Is it likely to be HIT? If so, what type? What are the options for anticoagulation in

this patient?

Back to the case…

Lab test ordered on 9/15 to determine presence of antibodies to heparinoid and PF4 complexes

On 9/16:– heparin was discontinued– Pt received blood transfusion (2 units)

On 9/17:– platelet count decreased to 65,000 platelets/μL.

On 9/18:– Serology testing revealed 48% heparin dependent platelet

antibiody reactivity– agatroban therapy was initiated.– platelet count rose to 80,000 platelets/μL

Patient’s platelet count continues to rise 122,000 platelets/μL

Back to the case…

What tests should be done in this patient?– Platelets– Serum reactivity

What is our patients 4 T’s Score?– Thrombocytopenia (1 point)+ Timing (0 points) + thrombosis or

other sequelae (0 points) + Other causes (1 point)= 2 points Is it likely to be HIT? If so, what type?

– 4 T’s score <3– Occurred within 2 days – Platelet count was trending down previously– Pt has hepatic insufficiency and coagulopathy issues

What other options for anticoagulation in this patient could be considered?

St. Luke’s Policy

References

Diaz, Josephina, et al. "Profiling of heparin-induced thrombocytopenia antibody levels in patients with and without diabetes." Clinical and applied thrombosis/hemostasis 16.2 (2010):121-5.

Franchini, Massimo. "Heparin-induced Thrombocytopenia: an Update." Thrombosis Journal. 04 Oct. 2005. Web. 20 Sept. 2010. <http://www.thrombosisjournal.com/content/3/1/14>.

Arepally, Gowthami M., and Thomas L. Ortel. "Heparin-Induced Thrombocytopenia." New England Journal of Medicine 355.8 (2006): 809-17. 24 Aug. 2006. Web. 20 Sept. 2010

Coutre, Steven. "Heparin-Induced Thrombocytopenia." UpToDate Inc. 28 Jan. 2008. Web. 23 Sept. 2010. <http://www.uptodate.com/online/content/topic.do?topicKey=coagulat/8950&selectedTitle=1~150&source=search_result>.

 DiPiro, Joseph T. "Hematologic Disorders." Pharmacotherapy: a Pathophysiologic Approach. New York: McGraw-Hill Medical, 2008. 1875-889. Print.

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